NUDT21 Links Mitochondrial IPS-1 to RLR-Containing Stress Granules and Activates Host Antiviral Defense

Aoyama-Ishiwatari, Saeko; Okazaki, Tomohiko; Iemura, Shun‐ichiro; Natsume, Tohru; Okada, Yasushi; Gotoh, Yukiko

doi:10.4049/jimmunol.2000306

Cited by 4 publications

(2 citation statements)

References 56 publications

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“…SGs can physically contact different membrane-bound organelles, including lysosomes or the ER, and starvation-induced SGs contact with mitochondria in human cells (Amen and Kaganovich, 2021; Lee et al, 2020; Liao et al, 2019). Furthermore, numerous mitochondrial proteins have been associated with SGs (Amen and Kaganovich, 2021; Aoyama-Ishiwatari et al, 2021; Paget et al, 2023). Our study identifies SGs as novel signalling components associated with the mammalian UPRmt and SG dynamics as a key for maintaining mitochondrial function during mitochondrial stress.…”

Section: Discussionmentioning

confidence: 99%

Activation of the mitochondrial unfolded protein response regulates the formation of stress granules

Lopez-Nieto,

Sun,

Relton

et al. 2023

Preprint

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To rapidly adapt to harmful changes to their environment, cells activate the integrated stress response (ISR). This results in an adaptive transcriptional and translational rewiring, and the formation of biomolecular condensates named stress granules (SGs), to resolve stress. In addition to this first line of defence, the mitochondrial unfolded protein response (UPRmt) activates a specific transcriptional programme to maintain mitochondrial homeostasis. We present evidence that SGs and UPRmt pathways are intertwined and communicate with each other. UPRmt induction results in eIF2α phosphorylation and the initial and transient formation of SGs, which subsequently disassemble. We show that the induction of GADD34 during late UPRmt protects cells from prolonged stress by impairing further assembly of SGs. Furthermore, mitochondrial respiration is enhanced during UPRmt activation when SGs are absent, suggesting that UPRmt-induced SGs have an adverse effect on mitochondrial homeostasis. These findings point to a novel crosstalk between SGs and the UPRmt that may contribute to restoring mitochondrial functions under stressful conditions.

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Section: Discussionmentioning

confidence: 99%

Activation of the mitochondrial unfolded protein response regulates the formation of stress granules

Lopez-Nieto,

Sun,

Relton

et al. 2023

Preprint

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“…Saeko et al. demonstrated the cytoplasmic localization of NUDT21 and its unexpected role in regulation of antiviral proteins in the cytoplasm in addition to its well-established localization to nucleus and function in alternative polyadenylation ( 92 ). According to the research, Masamha et al.…”

Section: Nudt21 and Apa And Tumormentioning

confidence: 99%

Relationship between NUDT21 mediated alternative polyadenylation process and tumor

Xiao

Gu²,

Deng³

et al. 2023

Front. Oncol.

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Alternative polyadenylation (APA) is a molecular process that generates diversity at the 3’ end of RNA polymerase II transcripts from over 60% of human genes. APA and microRNA regulation are both mechanisms of post-transcriptional regulation of gene expression. As a key molecular mechanism, Alternative polyadenylation often results in mRNA isoforms with the same coding sequence but different lengths of 3’ UTRs, while microRNAs regulate gene expression by binding to specific mRNA 3’ UTRs. Nudix Hydrolase 21 (NUDT21) is a crucial mediator involved in alternative polyadenylation (APA). Different studies have reported a dual role of NUDT21 in cancer (both oncogenic and tumor suppressor). The present review focuses on the functions of APA, miRNA and their interaction and roles in development of different types of tumors.NUDT21 mediated 3’ UTR-APA changes can be used to generate specific signatures that can be used as potential biomarkers in development and disease. Due to the emerging role of NUDT21 as a regulator of the aforementioned RNA processing events, modulation of NUDT21 levels may be a novel viable therapeutic approach.

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Gadd45β is critical for regulation of type I interferon signaling by facilitating G3BP-mediated stress granule formation

Chathuranga,

Nikapitiya,

Kim

et al. 2023

Cell Reports

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NUDT21 Links Mitochondrial IPS-1 to RLR-Containing Stress Granules and Activates Host Antiviral Defense

Cited by 4 publications

References 56 publications

Activation of the mitochondrial unfolded protein response regulates the formation of stress granules

Activation of the mitochondrial unfolded protein response regulates the formation of stress granules

Relationship between NUDT21 mediated alternative polyadenylation process and tumor

Gadd45β is critical for regulation of type I interferon signaling by facilitating G3BP-mediated stress granule formation

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